Side-chain crystallizable polymers for medical applications

ABSTRACT

Side-chain crystallizable (SCC) polymers are useful in various medical applications. In certain applications, heavy atom containing side-chain crystallizable polymers (HACSCCP&#39;s) are particularly useful. An example of a HACSCCP is a polymer that comprises a main chain, a plurality of crystallizable side chains, and a plurality of heavy atoms attached to the polymer. In certain configurations, the heavy atoms are present in an amount that is effective to render the polymer radiopaque. A polymeric material that includes an HACSCCP may be fabricated into a medical device useful for at least partially occluding a body cavity. For example, such a medical device may be an embolotherapy product. A polymeric material that includes a SCC polymer may also be fabricated into other medical devices, such as stents.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application, and claims the benefit andpriority of, U.S. application Ser. No. 13/101,391, filed May 5, 2011,issued as U.S. Pat. No. 9,782,523, which is a divisional of U.S. patentapplication Ser. No. 11/335,771, filed Jan. 18, 2006, issued as U.S.Pat. No. 8,703,113, which is a continuation-in part of U.S. patentapplication Ser. No. 11/176,638, filed Jul. 7, 2005, issued as U.S. Pat.No. 7,939,611, which claims priority to U.S. Provisional PatentApplication No. 60/586,796, filed Jul. 8, 2004, each of which is herebyincorporated by reference in its entireties.

BACKGROUND Field of the Invention

This invention relates to side-chain crystallizable polymers, andparticularly to side-chain crystallizable polymers useful in medicalapplications.

Description of the Related Art

Polymeric materials are widely used in numerous applications. Forexample, therapeutic embolization is the selective blockage of bloodvessels or diseased vascular structures. Examples of polymericembolotherapy devices and reagents include embolic coils, gel foams,glues, and particulate polymeric embolic agents used, for example, tocontrol bleeding, prevent blood loss prior to or during a surgicalprocedure, restrict or block blood supply to tumors and vascularmalformations, e.g., for uterine fibroids, tumors (i.e.,chemo-embolization), hemorrhage (e.g., during trauma with bleeding) andarteriovenous malformations, fistulas (e.g., AVF's) and aneurysms.

Polymeric liquid embolic agents include precipitative and reactivesystems. For example, in a precipitative system, a polymer may bedissolved in a biologically acceptable solvent that dissipates uponvascular delivery, leaving the polymer to precipitate in situ. Reactivesystems include cyanoacrylate systems in which, e.g., a liquid monomericand/or oligomeric cyanoacrylate mixture is introduced to the vascularsite through a catheter and polymerized in situ. In this system,polymerization is initiated by the available water in the blood.

A number of technological applications involve the use of a polymer thatundergoes a transition upon a change in temperature. For example, in themedical field, one way to introduce a solid polymer into a particularbody region is to heat the polymer into a flowable state, then injectthe polymer into the region and allow it to cool and solidify. U.S. Pat.No. 5,469,867 discloses side-chain crystallizable polymers that are saidto be useful for occluding channels in a living mammal. Such polymersare said to be designed such that they can be melted so that they areflowable slightly above body temperature but solidify when cooled tobody temperature.

SUMMARY

An embodiment provides a polymer that includes a main chain, a pluralityof crystallizable side chains, and a plurality of heavy atoms attachedto the polymer. The heavy atoms may be present in an amount that iseffective to render the polymer radiopaque. In an embodiment, thepolymer comprises a recurring unit of the formula (VI) as set forthbelow. Another embodiment provides a medical device that comprises sucha polymer.

Another embodiment provides a medical device that includes a polymericmaterial, the polymeric material comprising a biocompatible inherentlyradiopaque side chain crystallizable polymer. In an embodiment, themedical device comprises at least a stent.

Another embodiment provides a method of treatment that includesintroducing a medical device into a body cavity of a mammal in an amountthat is effective to at least partially occlude the body cavity, whereinthe medical device comprises a polymeric material, and wherein thepolymeric material comprises a side chain crystallizable polymer. In anembodiment, the method further includes forming a channel through themedical device.

Another embodiment provides a method for making an inherently radiopaqueside chain crystallizable polymer, comprising copolymerizing a firstmonomer and a second monomer, the first monomer comprising a heavy atomand the second monomer comprising a crystallizable group.

Another embodiment provides a method for making an inherently radiopaqueside chain crystallizable polymer, comprising reacting a side chaincrystallizable polymer with a heavy metal reagent under conditionsselected to attach a plurality of heavy atoms to the side chaincrystallizable polymer.

Another embodiment provides a stent that comprises a side chaincrystallizable polymer.

These and other embodiments are described in greater detail below.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a detailed view of a slide-and-lock stent configuration inaccordance with one preferred embodiment of the present invention,comprising deflectable teeth which deflect downward to provide a stentexhibiting mono-directional expansion.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

An embodiment provides a heavy atom-containing side-chain crystallizablepolymer (“HACSCCP”). Many polymers contain relatively low atomic numberatoms such as hydrogen, carbon, nitrogen, oxygen, silicon and sulfur.However, it has been found that the attachment of relatively higheratomic number atoms to the polymer may affect various physical andmechanical properties of the polymer. For example, attachment of heavyatoms to a polymer in sufficient amounts may advantageously render thepolymer easier to detect by various medical imaging techniques. The term“heavy atom” is used herein to refer to atoms having an atomic number of17 or greater. Preferred heavy atoms have an atomic number of 35 orgreater, and include bromine, iodine, bismuth, gold, platinum tantalum,tungsten, and barium. In certain configurations, HACSCCP' s may beinherently radiopaque. The term “inherently radiopaque” is used hereinto refer to a polymer to which a sufficient number of heavy atoms areattached by covalent or ionic bonds to render the polymer easier todetect by medical imaging techniques (e.g., by X-rays and/or duringfluoroscopy). HACSCCP' s may be used in a variety of applications,including medical applications in which they are configured to provide adegree of inherent radiopacity that may provide significant advantages.It will be understood that the degree to which the attached heavy atomsrender the polymer easier to detect by medical imaging techniques willgenerally depend on the amount of heavy atoms incorporated into thepolymer and the configuration (e.g., thickness) of the polymer.

In addition to heavy atoms, HACSCCP's also contain crystallizable sidechains. Side chain crystallizable (SCC) polymers, sometimes called“comb-like” polymers, are well-known, see N. A. Plate and V. P. Shibaev,J. Polymer Sci.: Macromol. Rev. 8:117-253 (1974), the disclosure ofwhich is hereby incorporated by reference. It will be understood thatHACSCCP' s are a type of SCC polymer, and that reference herein to SCCpolymers includes HACSCCP' s, unless otherwise stated. In an embodiment,the SCC polymer is substantially free of heavy atoms. HACSCCP's may beSCC polymers that have been modified to include heavy atoms, e.g., bybonding heavy atoms to an SCC polymer and/or by making a HACSCCP bypolymerizing monomers that contain heavy atoms. SCC polymers may havevarious configurations, e.g., homopolymer, copolymer (e.g., randomcopolymer, alternating copolymer, block copolymer, graft copolymer),various tacticities (e.g., random, isotactic, atactic, syndiotactic),etc. A SCC polymer may be a mixture or blend of two or more SCCpolymers, each of the individual SCC polymers in the mixture or blendhaving different configurations, different levels of heavy atom content,molecular weights, melting points, etc. The polymer backbone or mainchain of the SCC polymer, to which the crystallizable side chains areattached, may be configured in various ways, e.g., linear, branched,crosslinked, dendritic, single-stranded, double-stranded, etc. PreferredSCC polymers for medical applications are inherently radiopaque,biocompatible and/or bioresorbable. The heavy atoms may be attached tothe main chain and/or the side chains of a HACSCCP.

The crystallizable side chains of SCC polymers (including, e.g.,HACSCCP's) are preferably selected to crystallize with one another toform crystalline regions and may comprise, for example, —(CH₂)_(n)—and/or —((CH₂)_(m)—O—)_(n) groups. The side chains are preferably linearto facilitate crystallization. For SCC polymers that contain —(CH₂)_(n)—groups in the crystallizable side chain, n is preferably in the range ofabout 6 to about 30, more preferably in the range of about 20 to about30. For SCC polymers that contain—((CH₂)_(m)—O—)_(n) groups in thecrystallizable side chain, n is preferably in the range of about 6 toabout 30 and m is preferably in the range of about 1 to about 8. Morepreferably, m and n are selected so that the ((CH₂)_(m)—O—)_(n) groupscontain from about 6 to about 30 carbon atoms, even more preferably fromabout 20 to about 30 carbon atoms. The spacing between side chains andthe length and type of side chain are preferably selected to provide theresulting SCC polymer with a desired melting point. For example, formedical applications (e.g., embolotherapy), the spacing between sidechains and the length and type of the side chains are preferablyselected to provide the SCC polymer (and/or the material into which itis incorporated) with a melting point in the range of about 30° C. toabout 80° C. As the spacing between side chains increases, the tendencyfor the side chains to be crystallizable tends to decrease. Likewise, asthe flexibility of the side chains increases, the tendency for the sidechains to be crystallizable tends to decrease. On the other hand, as thelength of the side chains increases, the tendency for the side chains tobe crystallizable tends to increase. In many cases, the length of thecrystallizable side chain may be in the range of about two times toabout ten times the average distance between crystallizable side chainsof the SCC polymer.

Examples of SCC polymers include versions of the following polymers thatare selected so that the alkyl group is sufficiently long (e.g., greaterthan about 6 carbons) to provide the desired melting point and, forHACSCCP's, modified to include heavy atoms, e.g., sufficient heavy atomsto render them radiopaque: poly(1-alkene)s, poly(alkyl acrylate)s,poly(alkyl methacrylate)s, poly(alkyl vinyl ether)s, and poly(alkylstyrene)s. Examples of SCC polymers further include versions of thepolymers disclosed in the following references that include (or havebeen modified to include) crystallizable side chains and, for HACSCCP's,heavy atoms, e.g., sufficient heavy atoms to render them radiopaque:U.S. Pat. Nos. 4,638,045; 4,863,735; 5,198,507; 5,469,867; 5,912,225;and 6,238,687; as well as U.S. Provisional Patent Application No.60/601,526, filed 13 August 2004; all of which are incorporated byreference in their entireties, and particularly for the purpose ofdescribing SCC polymers and methods for making them.

In an embodiment, the side chains are selected to provide the SCCpolymer (or material into which the SCC polymer is incorporated) with acontrollable melting temperature. In a preferred embodiment, polymericembolotherapy products include HACSCCP' s configured to render theembolotherapy product detectable by a technique such as X-ray. The sidechains of the included HACSCCP may be selected so that the polymericembolotherapy product has a melting point higher than the bodytemperature of the mammal for which the product is intended. Such apolymeric embolotherapy product may, for example, be heated above themelting temperature to render it more flowable, thereby facilitatingdelivery to the target vasculature, where it may cool and solidify toembolize the vasculature. The use of inherently radiopaque HACSCCP' s toprovide radiopacity and a controlled melting point may be particularlyadvantageous in medical applications, but those skilled in the art willrecognize additional applications as well. Thus, while the variousdescriptions herein regarding the use of SCC polymers may indicate apreference for medical applications, it will be understood that varioustechnologies outside the medical area may also benefit from the use ofSCC polymers, and particularly HACSCCP's.

Furthermore, in some embodiments, the present SCC polymers may be usedto develop various medical devices. For instance, pre-fabricatedoff-the-shelf devices, rapidly prototyped devices, real-time prototypedevices using computer technology. Additionally present polymers may bedelivered directly to a non-lumen or non-cavity of the body. The variousmedical devices may include but are not limited to stents and stentgrafts for vascular and body lumen applications, pins, screws, sutures,anchors and plates for reconstructive skeletal or soft tissueapplications, cartilage replacements. SCC polymers may be placeddirectly in body tissue for example in subcutaneous and intramusculartissue.

An embodiment of a HACSCCP is a polymer comprising a main chain, aplurality of crystallizable side chains, and a plurality of heavy atomsattached to the polymer, the heavy atoms being present in an amount thatis effective to render the polymer radiopaque. A polymer that comprisesa recurring unit of the formula (I) is an example of such an HACSCCP:

In formula (I), X¹ and X² are each independently selected from the groupconsisting of Br and I; y¹ and y² are each independently zero or aninteger in the range of 1 to 4; and A¹ is selected from the groupconsisting of

R³ is selected from the group consisting of C₁-C₃₀ alkyl, C₁-C₃₀heteroalkyl, C₅-C₃₀ aryl, C₆-C₃₀ alkylaryl, and C₂-C₃₀ heteroaryl; R⁴selected from the group consisting of H, C₁-C₃₀ alkyl, and C₁-C₃₀heteroalkyl; R¹ is

R⁵ and R⁶ are each independently selected from the group consisting of—CH═CH—, —CHJ¹-CHJ²-, and —(CH₂)_(a)—; a is zero or an integer in therange of 1 to 8; J¹ and J² are each independently selected from thegroup consisting of Br and I; and Z is an O or an S; and Q is acrystallizable group comprising from about 6 to about 30 carbon atoms,preferably from about 20 to about 30 carbon atoms. In an embodiment, Qis:

Polymers of the formula (I) may be prepared by modifying the generalmethods described in U.S. Provisional Patent Application No. 60/601,526,filed 13 Aug. 2004, to select the appropriate side chain length, sidechain spacing and halogen content.

It will be recognized that Q and/or R⁴ may comprise crystallizable sidechains, that each of X, J¹ and J² is a heavy atom, and that y may beadjusted so that the number of heavy atoms in the polymer is sufficientto render the polymer radiopaque. Q and R⁴ may each independentlycomprise units selected from the group consisting of —(CH₂)_(n1)— and—((CH₂)_(m1)—O—)_(n1); where ml and n1 are each independently selectedso that Q and/or R⁴ each independently contain from about 1 to about 30carbon atoms, preferably from about 6 to about 30 carbon atoms, and morepreferably from about 20 to 30 carbon atoms. Moreover, Q and R⁴ mayinclude other functional groups such as ester and amide, and/or heavyatoms such as iodine and bromine. Non-limiting examples of Q and R⁴ thusinclude —C_(n1)H_(2n1+1), —CO₂—C_(n1)H_(2n1+1), —CONH—C_(n1)H_(2n1+1),—(CH₂)_(n1)—Br, —(CH₂)_(n1)—I, —CO₂—(CH₂)_(n1)—Br, —CO₂—(CH₂)_(n1)—I,—CONH—CO₂—(CH₂)_(n1)—Br, and —CONH—CO₂—(CH₂)_(n1)—I. In an embodiment,R⁵ is —CH═CH— or —(CH₂)_(a)—; R⁶ is —(CH₂)_(a)—; and Q is an ester groupcomprising from about 10 to about 30 carbon atoms.

It will be understood that a polymer that comprises a recurring unit ofthe formula (I) may be a copolymer, e.g., a polymer of the formula (I)that further comprises recurring —R²-A²-units, where R² is selected fromthe group consisting of —(CH₂)_(n2)— and —((CH₂)_(n2); where m2 and n2are each independently selected so that R² contains from about 1 toabout 30 carbon atoms; and where A² is defined in the same manner as A¹above. Thus, an embodiment provides a polymer comprising recurring unitsof the formula (Ia):

In formula (Ia), X¹, X², y¹, y², R¹ and A¹ are defined as describedabove for formula (I); p and q may each be independently varied over abroad range to provide a polymer having the desired properties, e.g.,melting point, radiopacity, and viscosity, using routineexperimentation. In an embodiment, p and q are each independently aninteger in the range of 1 to about 10,000. It will be appreciated thatthe formula (I) units and —(R²-A²)-units in a polymer comprisingrecurring units of the formula (Ia) may be arranged in various ways,e.g., in the form of a block copolymer, random copolymer, alternatingcopolymer, etc.

Another embodiment of a HACSCCP (e.g., a polymer comprising a mainchain, a plurality of crystallizable side chains, and a plurality ofheavy atoms attached to the polymer, the heavy atoms being present in anamount that is effective to render the polymer radiopaque) comprises arecurring unit of the formula (II):

In formula (II), R⁷ is H or CH₃; A³ is a chemical group having amolecular weight of about 500 or less; and A³ bears at least one of theheavy atoms attached to the polymer. Non-limiting examples of A³ includemetal carboxylate (e.g., —CO₂Cs), metal sulfonate (e.g., —SO₄Ba),halogenated alkyl ester (e.g., —CO₂—(CH₂)_(b)—Br), halogenated alkylamide (e.g., —CONH—(CH₂)_(b)—Br), and halogenated aromatic (e.g.,—C₆H₄—I), where b is an integer in the range of about 1 to about 4. Inan embodiment, A³ comprises an aromatic group bearing at least onehalogen atom selected from the group consisting of bromine and iodine.In another embodiment, A³ comprises a chemical group of theformula-L₁-(CH₂)_(n3)-L₂-Ar¹, wherein L₁ and L₂ each independentlyrepresent a nullity (i.e., are not present), ester, ether or amidegroup; n3 is zero or an integer in the range of about 1 to about 30; andAr¹ comprises a halogenated aromatic group containing from about 2 toabout 20 carbon atoms. HACSCCP's that comprise a recurring unit of theformula (II) may be formed by polymerization of the correspondingmonomers or by post-reaction of appropriate polymeric precursors.HACSCCP's that comprise a recurring unit of the formula (II) may becopolymers that include additional recurring units.

Side chain A³ groups in a HACSCCP comprising a recurring unit of theformula (II) may be crystallizable and/or the HACSCCP comprising arecurring unit of the formula (II) may further comprise a secondrecurring unit that comprises a crystallizable side chain. Examples ofsuitable second recurring units having crystallizable side chainsinclude the following: poly(1-alkene)s, poly(alkyl acrylate)s,poly(alkyl methacrylate)s, poly(alkyl vinyl ether)s, and poly(alkylstyrene)s. The alkyl groups of the foregoing exemplary second recurringunits preferably contain more than 6 carbon atoms, and more preferablycontain from about 6 to about 30 carbon atoms. For example, in anembodiment, the second recurring unit is of the formula (III):

In formula (III), R⁸ is H or CH₃; L³ is an ester or amide linkage; andR⁹ comprises a C₆ to C₃₀ hydrocarbon group. HACSCCP's comprising arecurring unit of the formula (II) and a second recurring unit (such asa recurring unit of the formula (III)) may be formed by copolymerizationof the corresponding monomers and/or by post-reaction of appropriatepolymeric precursors.

Another embodiment of a HACSCCP (e.g., a polymer comprising a mainchain, a plurality of crystallizable side chains, and a plurality ofheavy atoms attached to the polymer, the heavy atoms being present in anamount that is effective to render the polymer radiopaque) comprises arecurring unit of the formula (IV), where A³ is defined above:

In formula (IV), A⁴ represents H or a group containing from about 1 toabout 30 carbons, e.g., a C₁-C₃₀ hydrocarbon. Side chain A³ and/or A⁴groups in a HACSCCP comprising a recurring unit of the formula (IV) maybe crystallizable and/or the HACSCCP comprising a recurring unit of theformula (IV) may further comprise a second recurring unit that comprisesa crystallizable side chain. For example, in an embodiment, the secondrecurring unit is of the formula (V), where R¹⁰ comprises a C₆ to C₃₀hydrocarbon group and R¹¹ represents H or a group containing from about1 to about 30 carbons, e.g., a C₁-C₃₀ hydrocarbon:

Another embodiment of a HACSCCP comprises a recurring unit of theformula (VI):

wherein R¹² is H or CH₃ and n4 is an integer in the range of about 1 toabout 1,000. In preferred embodiments, a HACSCCP comprising a recurringunit of the formula (VI) is biocompatible. In another embodiment, amedical device (e.g., a stent, catheter or any other medical devicedescribed herein) comprises a polymer that comprises a recurring unit ofthe formula (VI). Recurring units of the formula (VI) may be formed invarious ways. For example, a starting polymer comprising recurringhydroxyethylmethacrylate (HEMA) units may be provided, and at least aportion of those recurring hydroxyethylmethacrylate (HEMA) units may bereacted with caprolactone to form recurring units of the formula (VIa)having crystallizable poly(caprolactone) (PCL) groups in the side chainas illustrated in Scheme A below.

Polymerization of the caprolactone to form the crystallizable PCL groupsmay be conducted by using an appropriate catalyst, e.g., stannousoctoate. The melting point of the side chain (and the HACSCCP) may becontrolled by manipulating the degree of polymerization (n4) of the PCLgroups, e.g., by adjusting the relative amounts of HEMA recurring unitsand caprolactone monomer during polymerization, in a manner generallyknow to those skilled in the art. The melting point may also becontrolled by manipulating the spacing along the polymer backbonebetween PCL groups, e.g., by appropriate selection of the amount of HEMArecurring units in the starting polymer. In an embodiment, n4 is aninteger in the range of about 2 to about 10. Heavy atoms may be includedin a HACSCCP that comprises a recurring unit of the formula (VI) invarious ways, e.g., the HACSCCP may further comprise a recurring unit ofthe formula (II) as described above.

SCC polymers are not limited to those described above (e.g., not limitedto HACSCCP's comprising recurring units of the formulae (I) to (VI)),and further include versions of known polymers that have been modifiedto include side-chain crystallizable groups and/or sufficient heavyatoms to render the resulting polymer radiopaque. Those skilled in theart will understand that HACSCCP's may be prepared in various ways,e.g., by employing routine experimentation to modify known methods formaking SCC polymers to thereby incorporate heavy atoms into theresulting polymers. For example, inherently radiopaque versions of theside chain crystallizable polymers described in U.S. Pat. No. 5,469,867may be prepared by copolymerizing the corresponding monomers withmonomers that contain heavy atoms. U.S. Pat. No. 5,469,867 isincorporated by reference and particularly for the purpose of describingmonomers, polymers and methods of polymerization. Examples of suitablemonomers that contain heavy atoms are disclosed in Kruft, et al.,“Studies On Radio-opaque Polymeric Biomaterials With PotentialApplications To Endovascular Prostheses,” Biomaterials 17 (1996)1803-1812; and Jayakrishnan et al., “Synthesis and Polymerization ofSome Iodine-Containing Monomers for Biomedical Applications,” J. Appl.Polm. Sci., 44 (1992) 743-748. HACSCCP's may also be prepared bypost-reaction, e.g., by attaching heavy atoms to the polymers describedin U.S. Pat. No. 5,469,867. Specific examples of SCC polymers that maybe modified with heavy atoms to make HACSCCP's include the acrylate,fluoroacrylate, methacrylate and vinyl ester polymers described in J.Poly. Sci, 10.3347 (1972); J. Poly. Sci. 10:1657 (1972); J. Poly. Sci.9:3367 (1971); J. Poly. Sci. 9:3349 (1971); J. Poly. Sci. 9:1835 (1971);J.A.C.S. 76:6280 (1954); J. Poly. Sci. 7:3053 (1969); Polymer J. 17:991(1985), corresponding acrylamides, substituted acrylamide and maleimidepolymers (J. Poly. Sci.: Poly. Physics Ed. 11:2197 (1980); polyolefinpolymers such as those described in J. Poly. Sci.: Macromol. Rev.8:117-253 (1974) and Macromolecules 13:12 (1980), polyalkyl vinylethers,polyalkylethylene oxides such as those described in Macromolecules 13:15(1980), alkylphosphazene polymers, polyamino acids such as thosedescribed in Poly. Sci. USSR 21:241, Macromolecules 18:2141,polyisocyanates such as those described in Macromolecules 12:94 (1979),polyurethanes made by reacting amine- or alcohol-containing monomerswith long-chain alkyl isocyanates, polyesters and polyethers,polysiloxanes and polysilanes such as those described in Macromolecules19:611 (1986), and p-alkylstyrene polymers such as those described inJ.A.C.S. 75:3326 (1953) and J. Poly. Sci. 60:19 (1962). The foregoingSCC polymers may be modified with heavy atoms to make HACSCCP's invarious ways. For example, monomers bearing heavy atoms may be preparedby iodinating and/or brominating the monomers used to make the foregoingpolymers. Those heavy atom-bearing monomers may then be copolymerizedwith the unmodified monomers to prepare HACSCCP's. Those skilled in theart may identify conditions for making the heavy atom-bearing monomersand corresponding HACSCCP's by routine experimentation.

In another embodiment, a HACSCCP is prepared by reacting a side chaincrystallizable polymer with a heavy metal reagent under conditionsselected to attach a plurality of heavy atoms to the side chaincrystallizable polymer. For example, the side chain crystallizablepolymer may be exposed to a heavy metal reagent that comprises bromineand/or iodine. Examples of heavy metal reagents include bromine vapor,iodine vapor, bromine solution and iodine solution. The side chaincrystallizable polymer may be exposed to the heavy metal reagent by,e.g., exposing or intermixing the solid polymer with heavy metal reagentand/or by dissolving or dispersing the side chain crystallizable polymerin a solvent and intermixing with the heavy metal reagent. Other methodsmay also be used.

SCC polymers may contain various amounts of heavy atoms and/orcrystallizable side chains, depending on the properties desired for theSCC polymer. Preferably, the content of crystallizable side chains issufficient to substantially reduce or prevent main chaincrystallization. In many cases, the amount of crystallizable side chainin the SCC polymer is in the range of about 20% to about 80% by weight,based on total polymer weight, and in some cases may be in the range ofabout 35% to about 65%, same basis. The length of the SCC polymercrystallizable side chain is preferably in the range of about two timesto about ten times the average distance between crystallizable sidechains. SCC polymers may comprise a crystalline region (e.g., formed bycrystallization of the side chains below the melting point of thepolymer) and a non-crystalline region (e.g., a glassy or elastomericregion formed by the non-crystallizable portions of the SCC polymer). Inan embodiment, the non-crystalline region has a glass transitiontemperature that is higher than the body temperature of a mammal, e.g.,higher than about 37° C.; in another embodiment, the non-crystallineregion has a glass transition temperature that is lower than the bodytemperature of a mammal, e.g., lower than about 37° C. The amount ofheavy atoms in a particular SCC polymer may be selected based on thedegree of radiopacity and/or material (mechanical) properties desired.For example, for medical applications, a HACSCCP preferably containsfrom about 1% to about 90% heavy atoms, more preferably about 20% toabout 50% by heavy atoms, by weight based on total weight of HACSCCP. Insome cases, the SCC polymer is incorporated into a polymeric materialand/or formed into a medical device as described below. When the SCCpolymer is a HACSCCP, the amount of heavy atoms in the HACSCCP may beadjusted to provide the resulting polymeric material and/or medicaldevice with the desired degree of radiopacity.

The indiscriminate incorporation of heavy atoms into side chaincrystallizable polymers often disrupts or prevents otherwisecrystallizable side chains from crystallizing, particularly when thelevels of heavy atom incorporation are high, the side chains arerelatively short, the side chains are relatively flexible, and/or thedistance between side chains is relatively large. Preferably, the heavyatoms are attached to the HACSCCP in a manner that minimizes oreliminates disruption of side chain crystallinity. For example, in anembodiment, at least about 50%, preferably at least about 80%, of theheavy atoms are attached to the main chain of the HACSCCP. In anotherembodiment, at least about 50%, preferably at least about 80%, of theheavy atoms are attached to the ends of the side chains of the HACSCCP,e.g., to the ends of the crystallizable side chains and/or tonon-crystallizable side chains. In another embodiment, at least about50%, preferably at least about 80%, of the heavy atoms are attached toeither the main chain or the side chains (crystallizable and/ornon-crystallizable) of the HACSCCP. In another embodiment, the HACSCCPis a block copolymer that comprises a crystalline block and an amorphousblock, and at least about 50%, preferably at least about 80%, of theheavy atoms are attached to the amorphous block.

The molecular weight of SCC polymers may be selected in view of theintended application for the polymer. For example, in some medicalapplications, e.g., for certain embolotherapy applications, it isdesirable for the SCC polymer to flow at temperatures higher than thepolymer melting point and to form a solid at temperatures below thepolymer melting point. The viscosity of a molten SCC polymer generallyincreases as the molecular weight of the polymer increases, and thus themolecular weight of a particular SCC polymer is preferably selected toprovide the desired molten polymer viscosity. For example, a suitablemolecular weight range for SCC polymers used in embolotherapy productsmay be in the range of from about 2,000 to about 250,000, preferablyfrom about 5,000 to about 150,000. Molecular weights are weight averageas determined by high pressure size exclusion chromatography using lightscattering detection.

In some cases, it may be desirable to mix or blend the SCC polymer witha second material (e.g., a second polymer) to form a polymeric material,which may then be employed in the intended application. For example, anembodiment provides a polymeric material that comprises a SCC polymer(e.g., a HACSCCP) and a second polymer. Preferably, the second polymeris biocompatible and/or bioresorbable. Examples of second polymerssuitable for mixing or blending with SCC polymers to form polymericmaterials include the non-inherently radiopaque polymers disclosed inU.S. Pat. No. 5,469,867 and the radiopaque polymers described in U.S.Provisional Patent Application No. 60/601,526, filed 13 Aug. 2004, bothof which are incorporated by reference. Depending on the intendedapplication, the relative amounts of SCC polymer and second polymer inthe polymeric material may vary over a broad range. For example, in anembodiment, a polymeric material comprises from about 1% to about 100%of a SCC polymer and up to about 99% of a second polymer, by weightbased on total. Since a polymeric material may consist solely of SCCpolymer, it will be appreciated that the term “polymeric material” asused herein includes SCC polymers (such as HACSCCP's). As noted above,it will be understood that the SCC polymer itself may be a mixture orblend of two or more individual SCC polymers, each having, for example,different molecular weights, configurations and/or melting points.

A polymeric material that comprises a SCC polymer may be formed intovarious configurations or pre-formed shapes, e.g., a rod, a particle, ora sheet. A rod may be linear, coiled, hollow, highly elongated (e.g., astring or strand), and may have various cross-sections shapes, e.g.,substantially round, substantially elliptical, substantially triangular,substantially rectangular, irregular, etc. A particle may be a sphericalparticle, a geometrically non-uniform particle (e.g., a flake or chip),a porous particle, a hollow particle, a solid particle, etc. A particlepreferably has a excluded diameter of from about 10 microns to about5,000 microns.

The configuration of the polymeric material may depend on variousfactors such as the intended application, shipping constraints,processing constraints, etc. For example, an embodiment provides amedical device that comprises a polymeric material. The polymericmaterial may comprise a SCC polymer. Non-limiting examples of medicaldevices that may comprise an SCC polymer include, for example, a stent(e.g., an expandable stent), stent graft, annuloplasty ring, vasculargraft, suture, vascular cuff, septal defect repair device, heart valve,heart valve component, heart valve repair device, closure device,inducer of vasculature and connective tissue proliferation, catheter(e.g., balloon catheter configured to deliver a stent) and/or a tissueengineered implant. Various medical device embodiments are described ingreater detail below. It will be appreciated that a medical device mayconsist solely of a polymeric material that consists solely of a SCCpolymer. For example, in an embodiment, a medical device is configuredto be deliverable (e.g., by injection, catheter, physical insertion,pouring, a heated rod, spraying and/or squirting) to a body cavity of amammal. Such a device may be, for example, an embolotherapy productformed primarily of a polymeric material that comprises a HACSCCP. Thus,while certain descriptions below may be directed to medical devices, itwill be understood that such descriptions also apply to polymericmaterials and to SCC polymers (including HACSCCP's), unless the contextindicates otherwise. Likewise, descriptions herein of polymericmaterials and of SCC polymers also apply to medical devices, unless thecontext indicates otherwise.

A medical device that comprises a SCC polymer may be a medical device inwhich at least a portion of the SCC polymer is positioned at a surfaceof the medical device. It has been found that such positioning of theSCC polymer at a surface of the medical device allows the surfaceproperties of the medical device to be manipulated as a function oftemperature, e.g., the SCC polymer at the surface may provide increasedbiocompatibility and/or function as a temperature-dependent lubricantand/or adhesive, e.g., at an interface with one or more other medicaldevices and/or medical device components. The SCC polymer may bepositioned at the surface of the medical device in various ways. Forexample, amounts of a SCC polymer may be applied to selected locationson the surface of the medical device; a SCC polymer may be coated ontothe surface of a medical device; a film of SCC polymer may be applied toa medical device; and/or a medical device may be manufactured in such away that a SCC polymer is formed at a surface. For example, in anembodiment, radiopaque and/or crystallizable groups may be grafted ontothe surface of a polymeric medical device, e.g., by reacting radiopaqueand/or crystallizable groups with functional groups on the surfaceand/or by polymerizing radiopaque and/or crystallizable monomers frominitiation sites on the surface to thereby form polymeric radiopaqueand/or crystallizable groups. Functional groups and initiation sites maybe created on the surface of a polymeric medical device in various ways.For example, treatment of a polymer surface with ionizing radiation(e.g., e-beam and/or gamma radiation) and/or plasma in the presence ofoxygen may result in the formation of —OH groups on the polymer surface.Such —OH groups may then be reacted with an isocyanate-functionalizedradiopaque and/or crystallizable group to thereby attach those groups tothe surface by forming urethane linkages. Polymerization of anappropriate monomer such as caprolactone may be initiated from the —OHgroups in the presence of a suitable catalyst (such as stannous octoate)to form crystallizable PCL groups that are attached to the polymersurface. As another example, treatment of a polymer surface withionizing radiation and/or plasma may produce active surface sitescapable of initiating the polymerization of photo- and/orradiation-sensitive crystallizable monomers (1-alkenes containing fromabout 6 to about 30 carbons), thereby grafting a side-chaincrystallizable polymer onto the surface of the polymeric medical device.The group attached to the surface may be radiopaque and/orcrystallizable. In an embodiment, the polymeric medical device comprisesa SCC polymer attached to the surface thereof.

The temperature-dependent properties (e.g., adhesion, lubrication, etc.)of a particular SCC polymer positioned at a surface of a medical devicetypically depend on the nature of the surface, the nature of the SCCpolymer and the nature of the interactions between them. For example, insome cases, relatively low molecular weight SCC polymers tend to havebetter adhesive properties at temperatures above the melting point ofthe SCC polymer, as compared to the adhesive properties of those SCCpolymers at temperatures below the melting point. On the other hand, insome cases, relatively high molecular weight SCC polymers tend to havebetter adhesive properties at temperatures below the melting point thanat temperatures above the melting point. Relatively non-polar SCCpolymers capable of forming relatively weak intermolecular interactions,such as heavily fluorinated SCC polymers, tend to be better lubricantsthan relatively polar SCC polymers capable of forming relatively strongintermolecular interactions, depending on the nature of the surface ofthe medical device. The use of a particular SCC polymer to providetemperature-dependent functionality at a surface of a medical device ispreferably determined by routine experimentation, in view of generalprinciples of adhesion known to those skilled in the art as informed bythe guidance provided herein.

A medical device that comprises a polymeric material may include one ormore additional components, e.g., a plasticizer, a filler, acrystallization nucleating agent, a preservative, a stabilizer, aphotoactivation agent, etc., depending on the intended application. Forexample, in an embodiment, a medical device comprises an effectiveamount of at least one therapeutic agent and/or a magnetic resonanceenhancing agent. Non-limiting examples of preferred therapeutic agentsinclude a chemotherapeutic agent, a non-steroidal anti-inflammatory, asteroidal anti-inflammatory, and a wound healing agent. Therapeuticagents may be co-administered with the polymeric material. In apreferred embodiment, at least a portion of the therapeutic agent iscontained within the polymeric material. In another embodiment, at leasta portion of the therapeutic agent is contained within a coating on thesurface of the medical device.

Non-limiting examples of preferred chemotherapeutic agents includetaxanes, taxinines, taxols, paclitaxel, dioxorubicin, cis-platin,adriamycin, and bleomycin. Non-limiting examples of preferrednon-steroidal anti-inflammatory compounds include aspirin,dexamethasone, ibuprofen, naproxen, and Cox-2 inhibitors (e.g.,Rofexcoxib, Celecoxib and Valdecoxib). Non-limiting examples ofpreferred steroidal anti-inflammatory compounds include dexamethasone,beclomethasone, hydrocortisone, and prednisone. Mixtures comprising oneor more therapeutic agents may be used. Non-limiting examples ofpreferred magnetic resonance enhancing agents include gadolinium saltssuch as gadolinium carbonate, gadolinium oxide, gadolinium chloride, andmixtures thereof.

Nucleating agents are materials that, in the presence of a polymer, makecrystallization of the polymer more thermodynamically favorable. Forexample, a nucleating agent may accelerate polymer crystallization at agiven temperature and/or induce crystallization (e.g., of a supercooledpolymer) at a higher temperature than in the absence of the nucleatingagent. Non-limiting examples of preferred nucleating agents include lowmolecular weight analogs of the SCC polymers with higher peakcrystallization temperatures than the bulk polymer being crystallized,carboxylate salts (such as sodium benzoate), inorganic salts (such asbarium sulfate) and various particulate materials with relatively highsurface area to volume ratios.

The amounts of additional components present in the medical device arepreferably selected to be effective for the intended application. Forexample, a therapeutic agent is preferably present in the medical devicein an amount that is effective to achieve the desired therapeutic effectin the patient to whom the medical device is administered or implanted.Such amounts may be determined by routine experimentation. In certainembodiments, the desired therapeutic effect is a biological response. Inan embodiment, the therapeutic agent in the medical device is selectedto promote at least one biological response, preferably a biologicalresponse selected from the group consisting of thrombosis, cellattachment, cell proliferation, attraction of inflammatory cells,deposition of matrix proteins, inhibition of thrombosis, inhibition ofcell attachment, inhibition of cell proliferation, inhibition ofinflammatory cells, and inhibition of deposition of matrix proteins. Theamount of magnetic resonance enhancing agent in a medical devices ispreferably an amount that is effective to facilitate radiologic imaging,and may be determined by routine experimentation.

The viscosity and/or melting point of a medical device that comprises aSCC polymer typically depends on the relative amounts of the SCC polymerand other components, if any, present in the medical device. Theviscosity and/or melting point of the medical device (or polymericmaterial in the medical device) may be controlled by manipulating theamount of SCC polymer in the medical device and by selecting a SCCpolymer that provides the resulting medical device with the desiredviscosity and/or melting point. Thus, for example, to provide apolymeric material that has a melting point of 40° C., it may bedesirable to select a SCC polymer that has a somewhat higher meltingpoint, e.g., about 45° C., for incorporation into the polymericmaterial, to compensate for the presence of a second polymer or othercomponent that has a tendency to lower the melting point of the SCCpolymer when in admixture with it. In an embodiment, a medical devicecomprises a polymeric material that has a melting point in the range ofabout 30° C. to about 80° C.

The polymeric material of the medical device is preferably configured toflow at a temperature above the melting point. The viscosity of thepolymeric material at the temperature above the melting point may varyover a broad range, depending on factors such as the intendedapplication. For example, for embolotherapy products, the polymericmaterial preferably has a viscosity above the melting point that allowsthe medical device to be delivered to the target vasculature by aconvenient technique such as by injection through a syringe and/or byflowing through a catheter. In such cases, the desired viscosity oftendepends on the diameter of the syringe needle or catheter, e.g., lowerviscosities are typically preferred at smaller diameters. On the otherhand, if the viscosity is too low, the polymeric material may migrateaway from the target vasculature prior to cooling and solidifying. In anembodiment, the polymeric material of the medical device has a viscosityin the range of about 50 cP to about 500 cP at the temperature above themelting point. In another embodiment, the polymeric material has aviscosity in the range of about 500 cP to about 5,000 cP at thetemperature above the melting point. In another embodiment, thepolymeric material has a viscosity in the range of about 5,000 cP toabout 250,000 cP at the temperature above the melting point. In anotherembodiment, the polymeric material has a viscosity in the range of about250,000 cP to about 1,000,000 cP at the temperature above the meltingpoint.

In an embodiment, the polymeric material is configured to form a solidmass upon delivery to a body cavity. The solid mass may wholly orpartially conform to an interior dimension of the body cavity. Forexample, the polymeric material may be configured to contain an amountof an SCC polymer that provides the polymeric material with a meltingpoint of about 40° C. The polymeric material may be further configuredto be deliverable to the body cavity, e.g., the polymeric material maybe in the form of a rod that may be heated to a molten state tofacilitate flow. The molten polymeric material may then be delivered toa body cavity by flowing through a delivery device in the molten state.Upon arrival in the body cavity, the molten polymeric material may atleast partially conform to the interior dimension of the body cavity,then cool to form a solid mass. As another example, the polymericmaterial may be in the form of small particles suspended in a relativelylow viscosity biocompatible carrier liquid such as water or saline. Thepolymeric material may then be caused to flow through a delivery deviceto the target body cavity. The small particle of polymeric material maybe heated prior to delivery, during delivery and/or within the targetcavity by, thereby causing the polymeric material to flow and conform toan interior dimension of the body cavity. Upon cooling, the polymericmaterial may form a solid mass that continues to conform to the interiordimension of the body cavity. It will be understood that polymericmaterials of various configurations and formulations before heating mayvary in their ability to conform to the body cavity once warmed and maytherefore be selected for this reason to tailor the treatment. Further,it will be understood that the polymeric material need not be completelymelted to achieve delivery. For example, a polymeric material may beformed into a particular shape, such as a coil, then implanted into thetarget body cavity while retaining the preformed shape. The polymericmaterial (e.g., coil) may be heated prior to and/or during implantationfor various reasons, e.g., to render the coil more resilient and thuseasier to deliver, and/or to enable the coil to better conform to thebody cavity into which it is implanted. The polymeric material may alsobe caused to flow outside the body then be delivered to the body cavityin a flowable state.

An embodiment provides a shape memory polymeric material that comprisesa SCC polymer. For example, a SCC polymer may be configured into a firstshape such as a coiled shape by a standard thermoplastic formationprocess and crosslinked to fix the memory of the first shape. The formedSCC polymer coil may then be heated to melt the SCC polymer, allowing itto be re-configured into a second shape such as a rod shape. Thecross-linking limits or prevents thermoplastic flow while the SCCpolymer is in the melted state. The SCC polymer while still in thesecond shape may then be cooled to a temperature at which the SCCpolymer recrystallizes. The recrystallization of the SCC polymer limitsor prevents the second shape (e.g., the rod shape) from returning to thefirst shape (e.g., the coil shape). Upon re-heating to a temperatureabove the melting point of the SCC polymer, the second shape returns tothe first shape, e.g., the rod reverts to its memory state of a coil.Crosslinking of the SCC polymer may be carried out in various ways knownto those skilled in the art.

An embodiment provides a method of treatment that comprises introducinga medical device as described herein (e.g., a medical device thatcomprises a SCC polymer) into a body cavity of a mammal in an amountthat is effective to at least partially occlude the body cavity. Ingeneral, such a method may be used to occlude any type body cavityincluding, e.g., various body cavities that may commonly be referred toas tubes, tubules, ducts, channels, foramens, vessels, voids, andcanals. In a preferred embodiment, the medical device is anembolotherapy product. Preferably, the SCC polymer is a HACSCCP. Inanother preferred embodiment, the body cavity comprises vasculature,e.g., an arteriovenous malformation or a blood vessel such as a varicosevein. The medical device may be introduced to the body cavity in avariety of ways, including by injection, by catheter and by surgicalimplantation. For a particular body cavity, the medical device ispreferably selected so that the polymeric material has a melting pointthat is sufficiently high that the polymer forms a solid mass at thenormal temperature of the body cavity, and sufficiently low so that thatsoftened or molten polymeric material may conform to a dimension of thebody cavity with little or no thermal damage to the mammal into which itis introduced. Introduction of such a polymeric material into the bodycavity thus may comprise heating the polymeric material to a temperaturethat is higher than the melting point and/or cooling it to a temperaturethat is lower than the melting point.

Various types of delivery devices may be used to introduce the medicaldevice to the body cavity, e.g., plastic tubes, catheters, fine cannula,tapered cannula and various types of syringes and hypodermic needleswhich are generally known to and available to those in the medicalprofession. An embodiment provides a medical apparatus that comprises apolymeric material and a delivery device, where the polymeric materialis an SCC polymer, and where the polymeric material and the deliverydevice are mutually configured to facilitate delivery of the polymericmaterial to a body cavity by the delivery device. The polymeric materialis preferably contained within the delivery device, in an amount thatmay vary somewhat depending on the particular body cavity to be occludedand the amount and type of occlusion desired. Those skilled in the artwill be aware of the size of the cavity being occluded based on the sizeof the patient, general knowledge of anatomy, and thus use of diagnosticmethods such as X-ray and MRI. Those skilled in the art will be able todetermine the amount of polymer material to be included within thedelivery device. In general, an excess amount of polymeric materialshould be included in the delivery device in order to provide for acertain margin of error. In an embodiment, the medical apparatuscomprises an embolotherapy product and a tube, where the embolotherapyproduct comprises a SCC polymer as described herein and where the tubeis configured to facilitate flow of the embolotherapy product to a bodycavity. For example, the tube may comprise a needle, cannula, syringe,and/or catheter, and may be equipped with a heater configured to heatthe embolotherapy product to a temperature above its melting point,e.g., to a temperature in the range of about 30° C. to about 80° C. Thepolymeric material may be included within the delivery device in a solidform or heated separately and provided in the delivery device in aflowable form. In one embodiment, the medical apparatus may beprepackaged with the polymeric material present within the deliverydevice and may thereafter be heated in order to make the polymericmaterial flowable. Heating may be applied from an exterior source suchas an air, water or oil bath or an electrical heater, in which case boththe delivery device and the polymeric material may be heated. Heatingcan also be applied from an interior source, e.g., using a smallelectrical resistive element at the end of a catheter through which athin rod of the solid polymeric material is passed, or using a smalllaser directed at the tip of a rod of polymeric material emerging fromthe end of a catheter.

The delivery device may include an extrusion nozzle which is preferablyrelatively small in diameter such that it will not seriously damage thetissue in the vicinity of the body cavity to be occluded, butsufficiently large such that the polymeric material can be readilyextruded from the nozzle. For example, in application that involves theocclusion of a body channel, the size of the nozzle is generally relatedto the inside diameter of the channel into which it is placed. Forexample, a 24 gauge needle typically fits within the opening of thepunctum which leads to the canaliculus. A 2 mm catheter is typicallyappropriate for introducing the polymeric material into the fallopiantubes. A ¼ inch cannula is preferred for introducing the polymericmaterial into the inner cavity of an adult humerus. When delivered inthe molten state, the polymeric material is preferably selected to havea viscosity that facilitates passage of the polymeric material throughthe extrusion nozzle. In general, relatively lower viscosities arepreferred for relatively smaller diameter nozzles.

It will be understood that the delivery device may include an extrusionnozzle with one or more delivery ports. The polymeric material may bedispensed through multiple ports serially or simultaneously. Thisapproach may accommodate better packing and/or stabilization of thepolymeric material that cools and it may allow for delivery of morepolymeric material across a large surface area. That variousconfigurations and formulations may be simultaneously delivered by theuse of various delivery ports.

For example, in an embodiment, two or more polymeric materials (eachcomprising a SCC polymer) may be delivered sequentially to a bodycavity. In an embolotherapy embodiment, a first polymeric material isdelivered to vascular structure. The first polymeric material may have afirst configuration, such as a coil. The coil may be preformed, e.g., ashape memory coil as described above that is delivered in a rod shape(forming a coil upon delivery), or may be a coil that is formed duringdelivery by extruding the polymeric material through a delivery port ofthe delivery device having an appropriately configured die. The firstpolymeric material is preferably delivered at a temperature higher thanits melting point, e.g., higher than the melting point of a first SCCpolymer in the first polymeric material.

A coil may be a relatively open structure that partially occludes thevascular structure, reducing the blood flow without completely stoppingit. Although such partial occlusion may be appropriate in some cases, inother cases further occlusion may be desired. Such further occlusion maybe accomplished by delivering a second polymeric to the vascularstructure in operable proximity to the first polymeric material. Thesecond polymeric material is preferably delivered at a temperaturehigher than the its melting point, e.g., higher than the melting pointof a second SCC polymer in the second polymeric material. The secondpolymeric material preferably has a lower viscosity than the firstpolymeric material, such that it may at least partially fill intersticesor gaps in the first polymeric material and/or between the firstpolymeric material and the interior of the vascular structure. Thus, forexample, the second polymeric material may have the consistency of apaste at a temperature above its melting point during delivery, allowingit to fill in the spaces of the first polymeric material coil.

One or more additional polymeric materials may be delivered to alocation in operable proximity to the first and second polymericmaterials. For example, the first and second polymeric materials mayonly partially occlude the vascular structure, although typically to agreater extend than the first polymer alone. In such a case, it may bedesirable to deliver a third polymeric material to provide furtherocclusion. The third polymeric material is preferably delivered at atemperature higher than its melting point, e.g., higher than the meltingpoint of a third SCC polymer in the third polymeric material. The thirdpolymeric material preferably has a lower viscosity than the firstpolymeric material, and more preferably lower than the second polymericmaterial, such that it may at least partially fill interstices or gapsin the polymeric mass formed by the first and second polymeric materialsand/or between the mass and the interior of the vascular structure.

Those skilled in the art will appreciate that multiple variations of theembodiments described above may be practiced. For example, a singlepolymeric material may be delivered in multiple doses or in differentforms, e.g., as a coil in a first delivery and as a paste in a seconddelivery, or as a paste in both the first and second deliveries. Two ormore polymeric materials may be delivered simultaneously, e.g., a firstpolymeric material in a coil shape may be coated or mixed with a secondpolymeric material in a paste or liquid form to form a composite thatcomprises both polymers, and the resulting composite may then bedelivered to the body cavity. Various body cavities may be the target ofthe delivery, and/or the order in which the various polymeric materialsand forms are delivered may be varied. Delivery of a polymeric materialthat comprises a SCC polymer may be combined, sequentially orsimultaneously, with the delivery of a different material, e.g., a metalembolic coil. Thus, for example, a polymeric material may be deliveredto a body cavity, and a metal embolic coil may be delivered to the bodycavity in contact with the polymeric material. Various periods of timemay pass between deliveries, e.g., a polymeric material coil may bedelivered to provide partial occlusion of a body cavity, and a secondpolymeric material paste may be delivered to a location in operableproximity to the coil minutes, hours, days, weeks, months, or yearslater.

For embodiments in which the polymeric material is delivered in themolten state, once a polymeric material has been included within thedelivery device and heated to a flowable state, the nozzle of thedelivery device (e.g., such as the tip of a needle, catheter, and/orsquirt nozzle) may be inserted into an opening of a channel (or throughthe wall of cavity) to be occluded and the polymer may be dispensed outof the nozzle into the body cavity. The injection is preferablycontinued until the desired amount of occlusion (e.g., vasculatureblockage) is obtained. In some instances, it may be desirable to occludeonly part of a cavity. Thereafter, the nozzle of the delivery device maybe withdrawn.

After the polymeric material has been delivered, the method may continuewithout operator interaction. For example, in the case of embolotherapy,the circulatory system of the mammal will typically cause a coolingeffect on the surrounding tissues which will cool the injected polymericmaterial. The polymeric material is preferably selected such that itcools and solidifies after losing only a small amount of energy, i.e.,hardens after decreasing in temperature by only a few degreescentigrade. Usually, cooling takes only a few seconds or minutes tooccur, although there are times when it may be desirable for cooling tooccur more slowly, e.g., in the case where a bone is reset afterdelivery. After cooling has taken place, the polymer preferablysolidifies within the cavity in a manner conforming to the shape of thecavity and the channel is at least partially filled or blocked. Thepolymeric material may remain in place in the cavity over long periodsof time. For preferred medical devices comprising biocompatible,non-immunogenic material, little or no adverse reaction is obtained. Incertain embodiment, the polymer is bioresorbable, and thus may diminishover time, in which case surrounding tissue may fill the previouslyoccluded region.

An effective cavity occlusion may also be achieved through the use ofSCC polymer material and various excipients. For instance, the SCCpolymer material may be delivered with (1) a photopolymerizable materialthat cross links through the use of a light; (2) a blood reactivesubstance that stimulates clotting such as collagen or thrombin, and/or(3) a nucleating agent.

In an embodiment, the polymeric material may be readily removed so as toagain provide a cavity which functions in a normal manner. For example,it may be desirable to remove the polymeric material from a vas deferensor fallopian tube to restore fertility. The polymeric material may beremoved in various ways. For example, the polymeric material may beremoved by simple mechanical extraction. In certain instances, devicessuch as forceps and/or catheters with various attachment prongsconnected thereto can be inserted into the channel and used to attach tothe polymeric material and pull the polymeric material out of the cavityor force it forward into a second cavity so that the first cavity is nolonger occluded and the polymeric material will not cause any damage.Alternatively, a device such as a heated wire may be brought intocontact with the solidified polymeric material. By heating the polymericmaterial with the heated wire, the temperature of the polymeric materialis raised above the melting point of the polymeric material so that itagain becomes flowable. In the case of a channel (such as a duct orvein), the heating may be continued until the flowable polymericmaterial flows from the channel and the channel is reopened to providenormal function. In certain circumstances, the liquid plug can be drawn,aspirated or forced out of a channel, e.g., by suction with a gentlevacuum or by using mild pressure created by air or a saline flow and/orby mechanical breakup along with trapping and aspiration.

A preferred method of removing the solidified polymeric material from achannel or other cavity is to inject a lipophilic material such as anaturally occurring oil or a fatty acid ester into the channel in thearea surrounding the solidified polymeric material. Preferably, alipophilic material is selected that has a tendency to diffuse into thepolymeric material, thereby reducing its melting point. The lipophilicmaterial is preferably added in an amount that is effective to reducethe melting point of the polymeric material below body temperature tosuch an extent that the polymer becomes flowable. Once the polymerbecomes flowable, the natural mechanical movement that occurs withinchannels of living beings will tend to move the polymer from thechannel, thereby restoring the normal function of the channel.

In a preferred embodiment, the medical device comprises a stent. Thestent may comprise various configurations, e.g., a configurationselected from the group consisting of a sheet stent, a braided stent, aself-expanding stent, a wire stent, a deformable stent, and aslide-and-lock stent.

In a preferred embodiment, the stent comprises at least twosubstantially non-deforming elements arranged to form a tubular member,the non-deforming elements being slidably interconnected for allowingthe tubular member to expand from a collapsed diameter to an expandeddiameter. In another variation the tubular member comprises a series ofslideably engaged radial elements and at least one locking mechanismwhich permits one-way sliding of the radial elements from a firstcollapsed diameter to a second expanded diameter.

A stent on a catheter is commonly collectively referred to as a stentsystem. Catheters include but are not limited to over-the-wirecatheters, coaxial rapid-exchange designs and the Medtronic ZipperTechnology that is a relatively new multi-exchange delivery platform.Such catheters may include, for instance, those described in U.S. Pat.Nos. 4,762,129; 5,232,445; 4,748,982; 5,496,346; 5,626,600; 5,040,548;5,061,273; 5,350,395; 5,451,233 and 5,749,888. Additional examples ofsuitable catheter designs include those described in U.S. Pat. Nos.4,762,129; 5,092,877; 5,108,416; 5,197,978; 5,232,445; 5,300,085;5,445,646; 5,496,275; 5,545,135; 5,545,138; 5,549,556; 5,755,708;5,769,868; 5,800,393; 5,836,965; 5,989,280; 6,019,785; 6,036,715;5,242,399; 5,158,548; and 6,007,545. The disclosures of the above-citedpatents are incorporated herein in their entirety by reference thereto.

Catheters may be specialized for various purposes such as to produce anultrasound effect, electric field, magnetic field, light and/ortemperature effect. Heating catheters may include for example thosedescribed in U.S. Pat. Nos. 5,151,100, 5,230,349; 6,447,508; and6,562,021 as well as WO 90\14046 A1. Infrared light emitting cathetersmay include for example those described in U. S. Patent Nos. 5,910,816and 5,423,321. The disclosures of the above-cited patents and patentpublications are incorporated herein in their entirety by referencethereto.

In another preferred variation, the stent further comprises an amount ofa therapeutic agent (for example, a pharmaceutical agent and/or abiologic agent) sufficient to exert a selected therapeutic effect. Theterm “pharmaceutical agent”, as used herein, encompasses a substanceintended for mitigation, treatment, or prevention of disease thatstimulates a specific physiologic (metabolic) response. The term“biological agent”, as used herein, encompasses any substance thatpossesses structural and/or functional activity in a biological system,including without limitation, organ, tissue or cell based derivatives,cells, viruses, vectors, nucleic acids (animal, plant, microbial, andviral) that are natural and recombinant and synthetic in origin and ofany sequence and size, antibodies, polynucleotides, oligonucleotides,cDNA's, oncogenes, proteins, peptides, amino acids, lipoproteins,glycoproteins, lipids, carbohydrates, polysaccharides, lipids,liposomes, or other cellular components or organelles for instancereceptors and ligands. Further the term “biological agent”, as usedherein, includes virus, serum, toxin, antitoxin, vaccine, blood, bloodcomponent or derivative, allergenic product, or analogous product, orarsphenamine or its derivatives (or any trivalent organic arseniccompound) applicable to the prevention, treatment, or cure of diseasesor injuries of man (per Section 351(a) of the Public Health Service Act(42 U.S.C. 262(a)). Further the term “biological agent” may include 1)“biomolecule”, as used herein, encompassing a biologically activepeptide, protein, carbohydrate, vitamin, lipid, or nucleic acid producedby and purified from naturally occurring or recombinant organisms,antibodies, tissues or cell lines or synthetic analogs of suchmolecules; 2) “genetic material” as used herein, encompassing nucleicacid (either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA),genetic element, gene, factor, allele, operon, structural gene,regulator gene, operator gene, gene complement, genome, genetic code,codon, anticodon, messenger RNA (mRNA), transfer RNA (tRNA), ribosomalextrachromosomal genetic element, plasmagene, plasmid, transposon, genemutation, gene sequence, exon, intron, and, 3) “processed biologics”, asused herein, such as cells, tissues or organs that have undergonemanipulation. The therapeutic agent may also include vitamin or mineralsubstances or other natural elements.

For devices placed in the vascular system, e.g., a stent, the amount ofthe therapeutic agent is preferably sufficient to inhibit restenosis orthrombosis or to affect some other state of the stented tissue, forinstance, heal a vulnerable plaque, and/or prevent rupture or stimulateendothelialization. The agent(s) may be selected from the groupconsisting of antiproliferative agents, anti-inflammatory, anti-matrixmetalloproteinase, and lipid lowering, cholesterol modifying,anti-thrombotic and antiplatelet agents, in accordance with preferredembodiments of the present invention. In some preferred embodiments ofthe stent, the therapeutic agent is contained within the stent as theagent is blended with the polymer or admixed by other means known tothose skilled in the art. In other preferred embodiments of the stent,the therapeutic agent is delivered from a polymer coating on the stentsurface. In another preferred variation the therapeutic agent isdelivered by means of no polymer coating. In other preferred embodimentsof the stent, the therapeutic agent is delivered from at least oneregion or one surface of the stent. The therapeutic may be chemicallybonded to the polymer or carrier used for delivery of the therapeutic ofat least one portion of the stent and/or the therapeutic may bechemically bonded to the polymer that comprises at least one portion ofthe stent body. In one preferred embodiment, more than one therapeuticagent may be delivered.

A preferred SCC polymer for use in the fabrication of a stent shouldfulfill at least some of the following criteria:

-   -   Radiopacity is preferably sufficient to ensure visibility of the        stent structure against the background of a human chest by X-ray        fluoroscopy, the standard method used in the clinic.    -   Stents according to aspects of the present invention are        preferably formed with walls for providing a low crossing        profile and for allowing excellent longitudinal flexibility. In        preferred embodiments, the wall thickness is about 0.0001 inches        to about 0.0250 inches, and more preferably about 0.0010 to        about 0.0100 inches. However, the wall thickness depends, at        least in part, on the selected material. For example, the        thickness may be less than about 0.0060 inches for plastic and        degradable materials and may be less than about 0.0020 inches        for metal materials. More particularly, for a 3.00 mm stent        application, when a plastic material is used, the thickness is        preferably in the range of about 0.0040 inches to about 0.0045        inches. However, a stent having various diameters may employ        different thicknesses for biliary and other peripheral vascular        applications. The above thickness ranges have been found to        provide preferred characteristics through all aspects of the        device including assembly and deployment. However, it will be        appreciated that the above thickness ranges should not be        limiting with respect to the scope of the invention and that the        teachings of the present invention may be applied to devices        having dimensions not discussed herein.    -   The stents are preferably hemocompatible to prevent acute        thrombosis. Accordingly, the device surfaces are preferably        resistant to protein adsorption and platelet/monocyte        attachment. Further, the device surfaces ideally favor        endothelial overgrowth but discourage attachment and growth of        smooth muscle cells (which are responsible for the occurrence of        restenosis).    -   Stents preferably maintain their mechanical strength (e.g., hoop        strength) for a period of about 1-24 months, more preferably        about 3-18 months, more preferably still about 3-12 months, and        most preferably about 3-6 months.

Stents preferably have a desirable biodegradation and bioresorptionprofile such that the stents reside for a period of time in the bodylumen such that at a later time any stent, bioresorbable or metal orother, may be used to re-treat the approximate same region of the bloodvessel or allow for other forms of vessel re-intervention such as vesselbypass.

In an embodiment, an SCC polymer-containing medical device comprises astent and/or a catheter, and thus an SCC polymer-containing medicaldevice may be a stent, or a stent system comprising a stent and adelivery catheter. The SCC polymer may be incorporated into such amedical device in various ways. For example, in various embodiments, thebody of the stent and/or catheter may comprise or consist essentially ofa SCC polymer; the stent and/or catheter may be coated with a SCCpolymer; the SCC polymer may be located at an interface between parts ofthe medical device, e.g., a between a stent and a catheter; the SCCpolymer may be a HACSCCP; and/or the SCC polymer may be positioned at asurface of the stent and/or catheter. In medical device embodiments, theSCC polymer is preferably biocompatible, and preferably has a meltingpoint in the in the range of about 30° C. to about 80° C.

A stent comprising a SCC polymer may be of any design (e.g.,slide-and-lock stents, sheet stents (sometimes referred to as jelly-rollstents), deformable stents, and self-expanding stents) suitable for agiven application. Preferably, a stent comprising an SCC polymer isdesigned to be readily implantable in the artery or tissue of an animal,such as a human, and to be expandable and/or suitable for holding openan artery, e.g., after said artery is opened via a medical procedure,such as an angioplasty. Examples of suitable stent designs for use inthe present invention include “slide-and-lock” stents, including thosedisclosed in U.S. Pat. Nos. 6,033,436; 6,224,626 and 6,623,521,co-pending U.S. patent application Ser. No. 11/016,269, filed Dec. 17,2004, and co-pending U.S. patent application Ser. No. 11/200,656, filedAug. 10, 2005, all of which are incorporated herein by reference.

With reference now to FIG. 1, a portion of a preferred stent embodiment320 is illustrated wherein radial elements 320(1), 320(2) are slidablyinterconnected. Each radial element is provided with a rail 328 having aplurality of deflectable teeth 326. Each of the teeth is angled upwardand is configured to deflect downward (i.e., in a radial direction). Asthe locking tabs 322, 324 slide along the deflectable teeth 326, theteeth are caused to deflect downward for allowing the tabs 322, 324 topass over the teeth 326 during deployment. However, due to the angle ofthe teeth, the locking tabs may only move in one direction. Moreparticularly, if a compressive force pushes the radial elements 320(1),320(2) back toward the collapsed condition, the locking tabs 322, 324will abut against the teeth 326, thereby preventing further relativemovement. All or some of the various elements (e.g., the elements320(1), 320(2), 322, 324, 326, 328) of the stent embodiment 320 maycomprise or consist essentially of a SCC polymer.

Other suitable stent designs adaptable for use herein include those usedtraditionally in metal and polymeric stents, including various mesh,jelly-roll, sheet, zigzag, and helical coil designs, e.g., thedeformable stents by Palmaz such as U.S. Pat. No. 4,733,665 and itssuccessors which have controllable expansion and a portion of theprosthesis that deforms with a force in excess of the elastic limit.Other stent designs include the following designs and their successors:U.S. Pat. No. 5,344,426 by Lau, U.S. Pat. Nos. 5,549,662 and 5,733,328by Fordenbacher, U.S. Pat. Nos. 5,735,872 and 5,876,419 by Carpenter,U.S. Pat. No. 5,741,293 by Wijay, U.S. Pat. No. 5,984,963 by Ryan, U.S.Pat. Nos. 5,441,515 and 5,618,299 by Khosravi, U.S. Pat. Nos. 5,059,211;5,306,286 and 5,527,337 by Stack, U.S. Pat. No. 5,443,500 by Sigwart,U.S. Patent No. 5,449,382 by Dayton, U.S. Patent No. 6,409,752 byBoatman, and the like.

Various temperature-dependent properties of the SCC polymer (e.g.,strength, flexibility, crystallinity, adhesion, etc.) may be manipulatedto enhance the performance of the medical device. For example, the stentmay be an expandable stent, e.g., a stent that is designed or configuredto have a changeable cross-sectional dimension, e.g., a cross-sectionaldimension that may be increased upon positioning of the stent within ablood vessel where expansion is desired. The stent may be mechanicallyexpandable, heat expandable, or it may be a hybrid stent that is bothmechanically and thermally expandable. In an embodiment, the body of theexpandable stent comprises an amount of SCC polymer that is effective toallow the stent to be expandable at a temperature above a melting pointof the SCC polymer. For example, the expandable stent may be positionedwithin the blood vessel, expanded at a temperature above a melting pointof the biocompatible inherently radiopaque side chain crystallizablepolymer, then cooled (actively or passively) to a temperature below themelting point. In an embodiment, at least a portion of the expandablestent is heat expandable. Preferably, the heat expandable portion isexpandable at a temperature above a melting point of the side chaincrystallizable polymer. In an embodiment, the expandable stent or aportion thereof comprises an amount of SCC polymer that is effective toallow the stent to be expandable at a temperature that is above bodytemperature (about 38° C.). For example, the stent may consistessentially of an SCC polymer having a melting point in the range ofabout 40° C. to about 80° C. Heating such a stent to a temperature abovethe melting temperature increases the flexibility of the stent, allowingit to assume the size and shape desired for adequate function, e.g.,support of the blood vessel. In an embodiment,

Prior to, during and/or after appropriate positioning within the bloodvessel, the expandable stent may be heated to a temperature above themelting point and expanded by, e.g., use of a balloon catheterpositioned within the stent, in a manner generally known to thoseskilled in the art. Optionally, a heated liquid may be circulatedthrough the balloon catheter to provide heating to the expandable stent.After expansion, the stent may be cooled, e.g., by allowing it to coolto the temperature of the surrounding blood and/or tissue, and/or bycirculating a cooling liquid through the balloon catheter. Upon coolingbelow the recrystallization temperature of the SCC polymer (which may bedifferent from or the same as the melting temperature), the stentbecomes much more rigid and thus capable of providing the desiredfunction, e.g., support of the blood vessel. The amount and type of SCCpolymer in the stent may be selected based on the temperature-dependentflexibility properties desired for the stent, as determined by routineexperimentation.

In an embodiment, the medical device (comprising a SCC polymer) is acatheter, e.g., a device having any of the catheter designs describedabove. The SCC polymer may be incorporated into such a catheter invarious ways, as discussed above. In an embodiment, at least a portionof the SCC polymer is positioned at a surface of the catheter. It hasbeen found that such positioning of the SCC polymer at a surface of thecatheter allows the surface properties of the catheter to be manipulatedas a function of temperature, e.g., the SCC polymer may function as atemperature-dependent lubricant and/or adhesive as discussed above.

In an embodiment, the medical device (comprising a SCC polymer) is astent system comprising a stent and a catheter. The SCC polymer may beincorporated into such a stent system in various ways, e.g., in the bodyor at a surface of the stent, in the body or at a surface of thecatheter, and/or at an interface between the stent and the catheter. TheSCC polymer may be positioned at an interface between two medicaldevices in various ways. For example, amounts of a SCC polymer may beapplied to selected locations on the surface of one or both of the stentand catheter; a SCC polymer may be coated onto one or both of thesurfaces of the stent and catheter; a film of SCC polymer may be appliedto one or both of the surfaces of the stent and catheter; and/or a oneor both of the surfaces of the stent and catheter may be manufactured insuch a way that a SCC polymer is formed at the surface(s). Methods forpositioning a SCC polymer at a surface and/or interface are describedabove.

In an embodiment, the SCC polymer is configured to providetemperature-dependent adhesion between the stent and the catheter. Forexample, as discussed above, a SCC polymer may be selected to providegreater adhesion at temperatures above the melting point of the SCCpolymer. Such a SCC polymer may be provided at an interface between thestent and the catheter and heated to temperature above the meltingpoint, thus increasing the amount of adhesion between the stent and thecatheter. The stent may then be positioned at the desired site withinthe vascular system. During such positioning, the adhesive properties ofthe SCC polymer desirably reduce or prevent slippage between the stentand catheter. After expansion of the stent, the SCC polymer may beallowed to cool (and/or actively cooled by circulating a liquid throughthe catheter) to a temperature below the melting point of the SCCpolymer. Upon such cooling, the adhesive character of the SCC polymer isreduced, allowing the catheter to be cleanly withdrawn from the vicinityof the stent without undesirable re-positioning of the stent. In otherembodiments, the SCC polymer is selected to provide greater adhesion attemperatures below the melting point of the SCC polymer. In suchembodiments, the stent is preferably positioned at a temperature belowthe melting point of the SCC polymer, while adhesion is greater (for theSCC polymer of this embodiment), expanded to the desired diameter withinthe vasculature, then heated to reduce the adhesion between the stentand catheter, thereby facilitating detachment and withdrawal of thecatheter while minimizing undesirable re-positioning of the stent. Thus,in some embodiments, the SCC polymer is heated to increase adhesionand/or cooled to decrease adhesion; in other embodiments the SCC polymeris cooled to increase adhesion and/or heated to decrease adhesion.Preferably, the SCC polymer is a HACSCCP.

In another embodiment, a medical device is formed in vivo by introducinga polymeric material into a body cavity, then forming a channel throughthe polymeric material. For example, a stent may be formed byintroducing a polymeric material (containing a SCC polymer) into a bloodvessel in a manner similar to that described above for embolization,then forming a channel through the polymeric material. Preferably, theSCC polymer is a HACSCCP. The channel is preferably substantiallycoaxial to the blood vessel, thus allowing blood to flow through thechannel. The channel may be formed in various ways. For example, in oneembodiment, the polymeric material is formed around a cylindrical mold.The SCC polymer in the polymeric material is selected so that theadhesion between the mold and the polymeric material is greater attemperatures below the melting point of the SCC polymer. The mold andpolymeric material are then inserted into the vasculature and positionedto at least partially occlude a blood vessel. The mold is then heated toa temperature slightly above the melting point of the polymericmaterial, thereby reducing adhesion between the polymeric material andthe mold. The mold is then withdrawn, leaving behind a cylindrical holein the polymeric material. Withdrawal of the mold without undesirablerepositioning of the polymeric material is facilitated by thetemperature-dependent adhesive properties of the SCC polymer. Othermethods may also be used to form channels in polymeric materials, e.g.,other mold shapes and configurations and/or by heating a portion of thepolymeric material to a temperature above the melting point of the SCCpolymer or polymeric material. The size, shape, number and configurationof the channels may be controlled in various ways. For example, heatenergy may be applied at various levels and in various forms, e.g., bylaser and/or by inserting heated implements (such as a heated wire) intothe polymeric material.

EXAMPLE 1

To a resin flask equipped with a thermometer, stirrer and refluxcondenser is added 500 grams (g) of octamethylcyclotetrasiloxane, 250 gof octaphenylcyclotetrasiloxane, and 250 g ofocta(iodophenyl)cyclotetrasiloxane, a heavy atom-bearing monomer. Theflask and contents are heated to 150° C. and 0.11 g of potassiumhydroxide-isopropanol complex (neutral equivalent=193.5) is added (Si:Kratio about 4470:1). The solution is allowed to stir for approximately30 minutes. Once the solution becomes too viscous to stir effectively(due to polymer formation), the polymer is heated to approximately 165°C. for 3 to 4 hours, then cooled to room temperature. The resultingpolymer is a HACSCCP comprising recurring units of the formula (IV) inwhich A³ and A⁴ are iodinated phenyl groups, recurring units of theformula (V) in which R¹⁰ and R¹¹ are phenyl groups, and dimethylsiloxanerecurring units.

EXAMPLE 2

To a resin flask equipped with a thermometer, stirrer, reflux condenserand 250 g of xylene stirred at approximately 135° C., a solution of 20 gof 4-iodo styrene, 60 g of docosanyl acrylate, and 11 g of di-tent-butylperoxide is added over a period of approximately 3 hours. After additionis complete, the mixture is allowed to continue stirring forapproximately another 3 hours to affect a more complete conversion, thencooled to room temperature. The resulting polymer is a HACSCCPcomprising recurring units of the formula (II) in which R⁷ and R⁸ are H,A³ is C₆H₄—I, and recurring units of the formula (III) in which L³ is anester linkage and R⁹ comprises a C₂₂ hydrocarbon group.

EXAMPLE 3

To a 500 mL 2-necked round-bottom flask equipped with a mechanicalstirrer and a rubber septum, 30 g of a monomer of the formula (VII)(I2DT-docosanyl) and 240 ml of methylene chloride are added. The solidsare dissolved with stirring. About 4.34 g of triphosgene dissolved in 30mL of methylene chloride is placed in a airtight syringe and added tothe reaction flask with a syringe pump at a constant rate over a periodof about 2 to 3 hours. The resulting viscous polymer solution is dilutedby adding about 150 mL of tetrahydrofuran and 10 mL of water. Thepolymer is isolated by precipitating the polymer solution inisopropanol, filtering the resulting solid and drying under vacuum. Thepolymer is a HACSCCP comprising a recurring unit of the formula (I) inwhich X¹ is I, y¹ is 2, y² is zero, A¹ is —(C═O)—, R⁵ is —CH₂CH₂—, R⁶ is—CH₂—, and Q is a crystallizable ester group containing 23 carbons.

EXAMPLE 4

An embolization is carried out as follows: A HACSCCP prepared asdescribed in Example 3 is formed into a rod-shaped embolic medicaldevice and loaded into a heated catheter. A physician delivers thecatheter to a Arteriovenous Fistula (AVF) to be embolized. A baselineangiogram is performed with fluoroscopy to better determine the regionto be embolized. The rod of HACSCCP embolic agent is pushed through thecatheter to the target site. Localized heating in the catheter melts theHACSCCP, allowing it to flow through the catheter and to the target sitein an liquid form that conforms to the AVF and embolizes the tissue. TheHACSCCP cools and recrystallizes at the target site. Delivery of theHACSCCP is continued until blood flow ceases in the target area. Bloodflow cessation is confirmed by injecting contrast agent and viewing byfluoroscopy. The HACSCCP is visible under fluoroscopy. The catheter iscooled to stop the flow of unneeded HACSCCP. The catheter is withdrawn.

EXAMPLE 5

An embolization is carried out as described in Example 4, except that ahigher viscosity HACSCCP is utilized and the HACSCCP is delivered to anartery for the treatment of an aneurysm. Embolization is achieved.

EXAMPLE 6

Embolization of a traumatic bleeding artery is carried out as generallydescribed in Example 4, except that, prior to delivery, the HACSCCP isformed into the shape of a coil and crosslinked by irradiation, therebyforming a memory coil. During heating, the memory coil softens and formsa flexible rod that is delivered to the artery through the catheter.Upon delivery, the flexible rod cools and resumes a coil shape withinthe artery, thereby reducing the blood flow.

EXAMPLE 7

Into a one-liter reactor is charged 90 grams of iodostyrene and 10 gramsof hydroxy ethyl methacrylate (HEMA). About 200 ml of the toluene(solvent) is added and the reactor is carefully purged with argon. Then0.5 mol percent of azobisisobutyronitrile (AIBN, polymerizationinitiator) is added and the reaction is brought to 70 degrees C. forabout 24 hours. The composition of the resulting copolymer of iodotyreneand HEMA is confirmed by nuclear magnetic resonance (NMR) spectroscopy.Then, 30 grams of caprolactone is added. To azeotropically dehydrate thereaction system, about 10% of the toluene is removed by distillation,and then 100 parts per million of stannous octoate catalyst is added.The temperature is raised to 100° C. and the caprolactone is polymerizedby grafting off the pendant hydroxyl groups of the iodostyrene/HEMAcopolymer. The resulting HACSCCP is coagulated in alcohol and dried. TheHACSCCP contains about 23% (NMR) semicrystalline polycaprolactone (PCL)in the form of crystallizable PCL side chains. The intrinsic viscosityof the HACSCCP is greater than 1.0 in toluene at 30° C., indicating arelatively high molecular weight.

EXAMPLE 8

A series of HACSCCP materials are prepared in a manner similar to thatdescribed in Example 7, except that the relative amounts of HEMA andiodostyrene are varied, along with the molecular weights of the backboneand PCL side chains. The series of HACSCCP polymers exhibits a range ofmelting points, depending on the length and spacing between the PCLcrystallizable side chains (longer lengths and/or closer spacingresulting in higher melting points, e.g., up to about 60° C.). Theseries of HACSCCP polymers also exhibits a range of radiopacities,depending on the number of iodostyrene recurring units incorporated intothe HACSCCP.

It will be appreciated by those skilled in the art that variousomissions, additions and modifications may be made to the materials andmethods described above without departing from the scope of theinvention, and all such modifications and changes are intended to fallwithin the scope of the invention, as defined by the appended claims.

What is claimed is:
 1. A method of treatment comprising: introducing amedical device into a body cavity of a mammal in an amount that iseffective to at least partially occlude the body cavity, and forming achannel through the medical device; wherein the medical device comprisesa polymeric material; and wherein the polymeric material comprises aninherently radiopaque, side chain crystallizable polymer.
 2. The methodof claim 1, wherein the polymeric material is introduced into the bodycavity in the presence of a mold.
 3. The method of claim 2, whereinforming the channel comprises removing the mold from the body cavity. 4.The method of claim 1, wherein the side chain crystallizable polymercomprises heavy atoms.
 5. The method of claim 1, wherein the side chaincrystallizable polymer is biocompatible.